PROJECT SUMMARY CANDIDATE: Daniel H. Craighead, PhD, is a postdoctoral fellow training in integrative physiology at the University of Colorado (CU) Boulder. In this K01 application, Dr. Craighead aims to determine the efficacy of high-resistance inspiratory muscle strength training (IMST), a novel and time-efficient lifestyle intervention, for lowering systolic blood pressure (SBP) and improving endothelial, cerebrovascular, and cognitive function. His immediate goal is to acquire the research training and professional skills necessary to transition to an independent, extramurally funded investigator. His long-term goal is to establish his own research program with a focus on identifying novel, evidence-based lifestyle interventions that lower blood pressure and prevent or delay the development of blood pressure-associated comorbidities and chronic diseases. CAREER DEVELOPMENT PLAN: Dr. Craighead's career development plan consists of: 1) acquiring new skills to assess cerebrovascular and cognitive function to support his proposed research plan; 2) train in new cellular and molecular techniques to assess changes in oxidative stress and nitric oxide-bioavailability; and 3) professional skill development through coursework; attendance/presentations at weekly journal clubs, CU seminars, and national scientific meetings; and regular interactions with his mentor team. ENVIRONMENT: The environment for Dr. Craighead's training plan will be outstanding. Dr. Craighead's primary mentor, Dr. Douglas Seals, and co-mentor, Dr. Michel Chonchol, are internationally recognized, NIH-funded scientists with strong records of successful mentoring in translational biomedical research. Co-mentor, Dr. Fiona Bailey, performed the pioneering work on high-resistance IMST, making her the foremost expert of this novel lifestyle intervention. Consulting mentor Dr. Zhiying You is Senior Biostatistician in the Department of Medicine at the CU Anschutz Medical Campus and regularly provides mentoring/consulting to trainees and faculty conducting clinical trials. Consulting mentor Dr. Philip Ainslie is the Canada Research Chair in Cerebrovascular Physiology with extensive experience assessing cerebrovascular function. Consulting mentor Dr. Brianne Bettcher is an Assistant Professor at the CU Anschutz Medical Campus and expert in assessing cognitive function. RESEARCH: Above-normal SBP is a highly prevalent condition, afflicting the majority of adults over age 50. Above-normal SBP increases the risk for developing cardiovascular diseases, stroke, cognitive decline, and other chronic conditions. This increased risk is largely attributable to the development of vascular dysfunction in the peripheral and cerebral arteries, secondary to an increase in oxidative stress and consequent reduction in nitric oxide-bioavailability. Healthy lifestyle practices are first-line therapies to lower SBP and decrease disease risk; however, adherence to these practices is poor due to their time-intensive nature. The proposed research will test the efficacy of time-efficient, high-resistance IMST for promoting adherence, lowering SBP, and improving endothelial, cerebrovascular, and cognitive function in adults with above-normal SBP.